Cutaneous squamous cell carcinoma is the second most common cutaneous malignancy with over 250,000 cases diagnosed per year. See M. Alam and D. Ratner, Cutaneous squamous cell carcinoma, 344 N ENG J MED 975-83 (2001). Although it is typically a straightforward diagnosis, there are many clinical and histologic simulants of cutaneous squamous cell carcinoma. Some of the lesions that can be the most difficult to differentiate, such as actinic keratosis and squamous cell carcinoma in-situ, display varying different degrees of keratinocyte dysplasia and are typically considered neoplastic precursors to squamous cell carcinoma. See B. R. Smoller, Squamous cell carcinoma: from precursor lesions to high-risk variants, 19 Suppl 2 MOD PATHOL (S88-92) (2006).
One of the most difficult lesions to differentiate from squamous cell carcinoma is pseudoepitheliomatous hyperplasia. Pseudoepitheliomatous hyperplasia is a hyperplastic squamoid proliferation typically associated with an inflammatory or neoplastic process. See M. H. Grunwald et al., Pseudocarcinomatous hyperplasia, 10 AM J DERMATOPATHOL 95-103 (1988); M. Zayour and R. Lazova, Pseudoepitheliomatous hyperplasia: a review, 33 AM J DERMATOPATHOL 112-22 (2011). Pseudoepitheliomatous hyperplasia can be seen in association with inflammatory infiltrates due to chronic ulceration with re-epithelialization, infection, and tattoo pigment. See M. H. Grunwald et al., Pseudocarcinomatous hyperplasia, 10 AM J DERMATOPATHOL 95-103 (1988); M. Zayour and R. Lazova, Pseudoepitheliomatous hyperplasia: a review, 33 AM J DERMATOPATHOL 112-22 (2011); N. Kluger et al., Pseudoepitheliomatous epidermal hyperplasia in tattoos: a report of three cases, 9 AM J CLIN DERMATOL 337-40 (2008). It has also been described in association with granular cell tumor, dermatofibroma, Spitz tumor, and melanoma. See M. H. Grunwald et al., Pseudocarcinomatous hyperplasia, 10 AM J DERMATOPATHOL 95-103 (1988); M. Zayour and R. Lazova, Pseudoepitheliomatous hyperplasia: a review, 33 AM J DERMATOPATHOL 112-22 (2011).
Histologically, pseudoepitheliomatous hyperplasia is characterized by irregular extension into the dermis by nests and strands of squamoid cells with jagged edges that may proliferate in a poorly circumscribed manner and display nuclear atypia and mitoses. Although morphologic criteria for differentiating between squamous cell carcinoma and pseudoepitheliomatous hyperplasia have been delineated, distinguishing between them may be difficult or nearly impossible in some circumstances especially in superficial, limited, or poorly oriented biopsies. See M. H. Grunwald et al., Pseudocarcinomatous hyperplasia, 10 AM J DERMATOPATHOL 95-103 (1988); M. Zayour and R. Lazova, Pseudoepitheliomatous hyperplasia: a review, 33 AM J DERMATOPATHOL 112-22 (2011); N. Kluger et al., Pseudoepitheliomatous epidermal hyperplasia in tattoos: a report of three cases, 9 AM J CLIN DERMATOL 337-40 (2008).
Because squamous cell carcinoma is one of the most commonly diagnosed cutaneous malignancies, because its accurate diagnosis is often challenging, and because clinical management of patients is largely dependent on pathologic diagnostic accuracy, there exists a need for a reliable method for accurately distinguishing between squamous cell carcinoma and pseudoepitheliomatous hyperplasia, thereby leading to accurate diagnoses and appropriate treatment.